Certain folate pathway enzymes have been implicated in infection and transformation by oncogenic viruses, and in other states of altered growth and cellular function. We are now measuring the simultaneous activities of 9 of the 15 major folate pathway enzymes in a variety of wild-type and mutant cells. The levels of folate pathway enzymes and the folate intermediates in various lines of untransformed cells are being compared with those in the corresponding lines transformed with DNA or RNA viruses. The changes in the folate pathways are being measured both during productive and nonproductive infections with DNA and RNA viruses, and during the transition of cells transformed by temperature-sensitive mutant viruses from the nonpermissive to the permissive temperature. Other studies aim to isolate mutant SV40 strains with enhanced effects on the folate pathway enzymes. We have found that certain malignant and virus-transformed cells require, in contrast to normal cells, small amounts of methionine in growth media containing homocysteine, folate and cobalamin despite high endogenous levels of methionine synthesis (PNAS 73: 1523-7, 1976). These transformed and malignant cells appear to be defective in methionine utilization rather than synthesis. The molecular basis of this phenomenon is presently being explored. The results of these studies should provide important new information regarding the biochemical and genetic bases of viral transformation, and the role of the folate pathways in growth altered states, as well as perhaps ultimately providing a basis for the development of effective cancer therapies. BIBLIOGRAPHIC REFERENCES: Erbe, R.W.: Inherited gastrointestinal polyposis syndromes. N. Engl. J. Med. 294: 1101-1104, 1976. Hoffman, R.M. and Erbe, R.W.: High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine. Proc. Nat. Acad. Sci. USA 73: 1523-1527, 1976.